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"Ansell, Mark"
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Non-smoking, non-drinking, oral squamous cell carcinoma patients are a distinct and clinically significant group
Purpose
Carcinogenesis of oral squamous cell carcinoma (OSCC) has long been associated with exposure to tobacco smoke and alcohol consumption. Some centres have reported that non-smoking non-drinking (NSND) patients represent a significant and increasing proportion of OSCC cases with reports of poorer outcomes. Demographic characteristics are variably reported for this group and carcinogenesis is not fully understood. We present the largest cohort study to date in this subject area and sought to better understand demographics and survival.
Methods
We interrogated 541 OSCC patients by retrospective analysis to assess risk factor status, disease characteristics and survival. Patients were categorised according to smoking and alcohol exposure with non-smoker (NS) status defined as less than five cigarettes per week with no history of use greater than this. Non-drinker (ND) status was defined as less than three standard drinks per week with no history of alcohol consumption greater than this. Those both NS and ND were categorised as NSND. Subsite, tumour stage and treatment were recorded along with evidence of cervical nodal and distant metastasis.
Results
These patients were more likely to be female, older and present with early-stage disease. Tumour site was tongue, maxillary alveolus and buccal mucosa, at variance with the smoker drinker groups.
Conclusion
NSNDs comprise a significant proportion our OSCC population. These patients were more likely to be female, older and present with early-stage disease. Tumour site was tongue, maxillary alveolus and buccal mucosa, at variance with the smoker drinker groups. Thus, NSNDs are a clinically distinct and significant group in oral cavity cancer management.
Journal Article
Management of Devastating Ocular Trauma - Experience of Maxillofacial Surgeons Deployed to a forward Field Hospital
Combat-related eye injuries continue to increase in frequency and are generally secondary to Improvised Explosive Devices. Many ocular injuries are potentially preventable by the wearing of ballistic eye protection. The management of penetrating eye trauma is normally outside the routine practice of maxillofacial surgeons in the UK. The aim of this paper is to describe the surgical techniques used in the modern management of devastating ocular trauma including selected case examples managed by British military maxillofacial surgeons deployed to Afghanistan.
Journal Article
Letter: Marketing Birmingham's role
It is incorrect to state that 'the report takes sideswipes at Marketing Birmingham'. In fact, the report acknowledges the role that Marketing Birmingham has to play in the city and highlights the success of our Championing Birmingham initiative, which has already encouraged 53 city organisations to promote the Birmingham advantage, demonstrating the cooperation between the city and its organisations.
Newspaper Article
The mode of inheritance of resistance to phosphine in two species of stored product beetles
The mode of inheritance of resistance to phosphine was investigated in two species of beetle pest of stored products, the lesser grain borer Rhyzopertha dominica and the rust red flour beetle Tribolium castaneum. Two resistant strains of each species (exhibiting high and low levels of resistance), as well as susceptible stocks, were studied. The highly resistant stocks of both species were as tolerant as any stocks of these species reported in the literature. A similar course was followed in the study of each resistant stock. The distributions of tolerances of the resistant and susceptible stocks were determined, as was that of a heterozygous F1 generation. Where possible, discriminating doses of phosphine were determined to differentiate between these three genotypes. These discriminating doses were applied to segregating (F2 and backcross) progenies and the response noted. This observed response was compared to that expected given that resistance was due to variation at one, two or many loci. High level resistance in both species was due to two independently segregating, autosomal loci. At one locus, the resistance allele was virtually recessive whilst at the second locus, the resistance allele was semidominant. Low level resistance in a stock of R.dominica was inherited as a single autosomal, recessive gene. This gene appeared allelic with a resistance gene present in the highly resistant stock. Studies with T.castaneum showed that the semidominant gene present in the highly resistant stock was linked to the marker gene, pearl. This association was also found in a second highly resistant stock. Low level resistance was linked to a different marker gene, missing abdominal sternites.
Dissertation
ON PITT'S TERMS
The success of the Pitt basketball program and the subsequent decline of the Penn State program has me wondering: When will the Pitt athletic department inform Penn State that in order to continue the basketball rivalry, Penn State must agree to play two games...
Newspaper Article
LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins
Cryo-electron microscopy (cryo-EM) enables the determination of membrane protein structures in native-like environments. Characterising how membrane proteins interact with the surrounding membrane lipid environment is assisted by resolution of lipid-like densities visible in cryo-EM maps. Nevertheless, establishing the molecular identity of putative lipid and/or detergent densities remains challenging. Here we present LipIDens, a pipeline for molecular dynamics (MD) simulation-assisted interpretation of lipid and lipid-like densities in cryo-EM structures. The pipeline integrates the implementation and analysis of multi-scale MD simulations for identification, ranking and refinement of lipid binding poses which superpose onto cryo-EM map densities. Thus, LipIDens enables direct integration of experimental and computational structural approaches to facilitate the interpretation of lipid-like cryo-EM densities and to reveal the molecular identities of protein-lipid interactions within a bilayer environment. We demonstrate this by application of our open-source LipIDens code to ten diverse membrane protein structures which exhibit lipid-like densities.
Interpretation of lipid-like densities in cryo-EM structures of membrane proteins is challenging. Here authors present LipIDens, enabling molecular dynamics analysis of protein-lipid interactions.
Journal Article
The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism
Hedgehog (HH) ligands, classical morphogens that pattern embryonic tissues in all animals, are covalently coupled to two lipids—a palmitoyl group at the N terminus and a cholesteroyl group at the C terminus. While the palmitoyl group binds and inactivates Patched 1 (PTCH1), the main receptor for HH ligands, the function of the cholesterol modification has remained mysterious. Using structural and biochemical studies, along with reassessment of previous cryo-electron microscopy structures, we find that the C-terminal cholesterol attached to Sonic hedgehog (Shh) binds the first extracellular domain of PTCH1 and promotes its inactivation, thus triggering HH signaling. Molecular dynamics simulations show that this interaction leads to the closure of a tunnel through PTCH1 that serves as the putative conduit for sterol transport. Thus, Shh inactivates PTCH1 by grasping its extracellular domain with two lipidic pincers, the N-terminal palmitate and the C-terminal cholesterol, which are both inserted into the PTCH1 protein core.
Cholesterol can function as both a substrate and an inhibitor of the Hedgehog receptor Patched. Structural analysis and molecular dynamics simulations reveal that cholesterol inhibits Patched by inserting into its extracellular domain
Journal Article
Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer
The addition of veliparib, a PARP inhibitor, to induction chemotherapy and maintenance therapy in women with advanced ovarian cancer significantly improved progression-free survival over induction chemotherapy alone without maintenance therapy. The improvement was especially notable in patients with mutated
BRCA
or homologous-recombination defects.
Journal Article